Nitrogen → tert-Butyl 3-(3-methylpyridin-2-yl)benzoate

Participants

Role	Name	HCID	Charge
Reactant	Nitrogen	HCID 947	—
Reactant	Dichloromethane	HCID 6344	—
Reactant	Methanesulfonic Acid	HCID 6395	—
Reactant	Potassium Carbonate	HCID 11430	—
Reactant	Sodium Hydroxide	HCID 14798	—
Reactant	2-Bromo-3-methylpyridine	HCID 220832	—
Reactant	(3-((Tert-butoxy)carbonyl)phenyl)boronic acid	HCID 2773299	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Solvent	Toluene	HCID 1140	—
Product	tert-Butyl 3-(3-methylpyridin-2-yl)benzoate	HCID 57516851	82%

Reaction Conditions

Temperature	80 °C

Reaction Steps

2-Bromo-3-methylpyridine (1.0 eq) is dissolved in toluene (12 vol). K2CO3 (4.8 eq) is added followed by water (3.5 vol) and the mixture heated to 65° C. under a stream of N2 for 1 hour. 3-(t-Butoxycarbonyl)phenylboronic acid (1.05 eq) and Pd(dppf)Cl2.CH2Cl2 (0.015 eq) are then added and the mixture is heated to 80° C. After 2 hours, the heat is turned off, water is added (3.5 vol) and the layers are allowed to separate. The organic phase is then washed with water (3.5 vol) and extracted with 10% aqueous methanesulfonic acid (2 eq MsOH, 7.7 vol). The aqueous phase is made basic with 50% aqueous NaOH (2 eq) and extracted with EtOAc (8 vol). The organic layer is concentrated to afford crude tert-butyl-3-(3-methylpyridin-2-yl)benzoate (82%) that is used directly in the next step.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09434717B2
Source dataset	uspto-grants-2016_09
ORD ID	ord-00a65a3ffaa5405e921719537369bf38
Source note	uspto-grants-2016_09